A variety of conventional capsules containing various active ingredients have been reported. Widely used materials of shells of these capsules include gelatin and agar. Since shells made of materials such as gelatin and agar disintegrate in the acidic environment of the stomach, it was not possible to use acid-labile substances as active ingredients.
Enteric capsules have been recently developed for this reason. Enteric capsules are capsules whose shells have acid resistance, therefore do not disintegrate in the stomach, but disintegrate in the intestines to release the capsule fills. These enteric capsules are used not only to encapsulate acid-labile substances as active ingredients, but also to encapsulate substances to be released slowly for effects sustained for a long period of time and substances that cause bad breath and flavor reversion when digested in the stomach, such as garlic and a fish oil.
Methods of manufacturing enteric capsules proposed so far include a method comprising (a) preparing a solution comprising a film-forming, water-soluble polymer and an acid-insoluble polymer and mixing with appropriate plasticizers to form a gel mass; (b) casting the gel mass into films or ribbons using heat-controlled drums or surfaces; and (c) forming a soft capsule using rotary die technology (see Patent Document 1).
Also proposed is a method of manufacturing an enteric, sustained-release soft capsule, comprising manufacturing a soft capsule material mixture obtained by homogeneously mixing and kneading gelatin, polyol as a plasticizer, an alkali metal salt, water, and a polysaccharide such as carrageenan, agar, or locust bean gum at a concentration of 6 to 40% by mass; and encapsulating at least one selected from garlic, a fish oil, propolis, an enteric bacterium, and a protein agent with the soft capsule material mixture (see Patent Document 2). However, since 2 or more polysaccharides are necessary and an alkali metal salt is necessary at the time of mixing and kneading, gelation with 2 polysaccharides is already promoted at the time of the capsule formation, causing a problem of very poor formability (very poor adhesiveness).
Further proposed is a method of manufacturing an enteric soft capsule, comprising a preparation step of preparing a capsule shell liquid comprising gelatin, water, a plasticizer, and 10 to 30 parts by weight of low methoxyl pectin having a degree of esterification of 20 to 40% per 100 parts by weight of gelatin; and a capsule-forming step of forming a soft capsule in which fill materials are packed into a capsule shell formed from the capsule shell liquid with a rotary die capsule-forming apparatus; wherein the capsule shell liquid comprises no salts comprising a polyvalent metal ion that gelates low methoxyl pectin and the method comprises no step of immersing the formed soft capsule in a gelation solution comprising the polyvalent metal ion (see Patent Document 3).